Made available in DSpace on 2014-06-12T23:00:03Z (GMT). No. of bitstreams: 2 arquivo2831_1.pdf: 2488118 bytes, checksum: 6319faa924393c55a7e426be9514dcdd (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2010 / Faculdade de Amparo à Ciência e Tecnologia do Estado de Pernambuco / Sabe-se que o etanol e a desnutrição podem produzir vários efeitos no Sistema Nervoso Central, tais como, microcefalia, deficiência mental, disfunção motora e deficiências cognitivas, no entanto, os mecanismos que induzem estas alterações permanecem desconhecidos ou pouco entendidos. Baseando-se nessas informações, o presente estudo avaliou os efeitos do etanol e desnutrição sobre a área e perímetro do soma, o número e a extensão dos prolongamentos primários dos neurônios NADPH-diaforase, bem como a densidade neuronal nas camadas corticais do córtex visual através de parâmetros morfométricos. Para tanto, estudou-se o córtex visual de ratos machos Wistar, com 40 dias de idade, gerados e amamentados por matrizes submetidas à dieta multicarencial (8% de proteína) e à administração de álcool (Aguardente comercial ou Etanol PA). Os animais foram distribuídos em seis grupos experimentais conforme o tratamento (N, D, AN, AD, EN e ED). Os cortes histológicos encefálicos foram corados pelo método Cresil Violeta - coloração de Nissl - e pelo método indireto da enzima málica para a marcação histoquímica das células NADPH diaforase. Houve modificação nos padrões morfológicos do córtex visual de ratos, observando-se que: a) a desnutrição não influenciou a densidade neuronal, porém em relação aos neurônios NADPH-diaforase, encontrou-se redução na densidade, área, perímetro, extensão e número dos prolongamentos; b) o tratamento com álcool isoladamente ou associado à desnutrição teve influência sobre a densidade neuronal, bem como na área, perímetro, extensão dos prolongamentos e densidade dos neurônios NADPH-diaforase positivos, porém não influenciou no número de prolongamentos. Concluiu-se que o álcool e a desnutrição, de forma isolada ou em associação, influenciaram o perfil morfológico de neurônios córtex visual durante o desenvolvimento perinatal de ratos jovens

Orientador: Sylvia Maria Ciasca / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-04T02:33:43Z (GMT). No. of bitstreams: 1 Souza_ReginaCeliaTurollade_D.pdf: 5836282 bytes, checksum: 7762f485e24cf5a1570c237e53078885 (MD5) Previous issue date: 2004 / Resumo: o presente estudo teve como objetivo caracterizar o desempenho da Função Motora e Sensorial da criança com paralisia cerebral hemiparética e correlacionar os resultados encontrados aos achados. do exame de neuroimagem. Foram selecionados 46 sujeitos, de . ambos os sexos, na faixa etária de sete a dezesseis anos de idade, sendo 23 com paralisia cerebral hemiparética de etiologia pré e/ou perinatal (Grupo 1) e 23 sujeitos normais (Grupo ll). Foram utilizados protocolos para avaliação das funções motora e sensorial, que avaliam a função motora grosseira, força muscular e amplitude de movimento, exame neurológico, função motora fina, função sensorial e percepção (BECKUNG, 2000), exame de ressonância magnética (RM) e protocolos para análise da lesão na neuroimagem (OKUMURA et alo 1997a.b, modificado por PIOVESANA, 1999). Os sujeitos de GI foram selecionados em banco de dados do ambulatório de paralisia cerebral e avaliados no serviço de fisioterapia e terapia ocupacional do Hospital de Clínicas, Universidade Estadual de Campinas (UNICAMP). Após consentimento dos pais através do Termo de Consentimento Livre e Esclarecido, todos os sujeitos foram submetidos às avaliações clínicas através dos instrumentos propostos. Crianças co.m PC-H com deformidade músculo esquelética limi~te, deficiência mental grave, deficiência visual ou auditiva incapacitante não fizeram parte dessa pesquisa. O desenho do estudo foi descritivo e de corte transversal. As informações obtidas foram armazenadas através de banco de dados do programa EPI-INFO 6.02 (Epidemiological Information) para posterior análise estatística. A comparação do desempenho das funções motora e sensorial entre os grupos foi realizada através do Teste de Wilcoxon para amostras relacionadas demonstrando que o grupo propósito apresentou disfunção leve na média total do exame em todos os subitens: função motora grosseira, força muscular e amplitude de movimento (p < 0,001), exame neurológico (p < 0,001), função motora fina (p < 0,001), função sensorial (p < 0,001) e percepção (p = 0,0002). Para comparação de medidas continuas ou ordenáveis entre grupos independentes foram utilizados os Testes de Mann-Whitney e Kruskal- Wallis. Comparando o desempenho da função motora e sensorial entre as categorias com a extensão da lesão, verificou-se melhor desempenho da função motora grossa nos sujeitos com lesões atingindo uma única estrutura encefálica aos com lesões bilaterais (p = 0,0122 Teste de Kruskall-Wallis). No exame neurológico, sujeitos com lesão atingindo uma única estrutura apresentaram melhores resultados que os sujeitos com lesões atingindo duas estruturas sencefálicas e lesões bilaterais (p = 0,0066 Teste de Kruskall-Wallis). Na função motora fina, sujeitos com lesão atingindo uma única estrutura enceralica demonstraram melhores resultados que os sujeitos com lesões atingindo duas estruturas encefálicas (p = 0,02755 Teste de Kruskall-Wallis). COlTelacionando o desempenho da função motora e sensorial à localização da lesão, constatou-se que os sujeitos com lesões subcorticais apresentaram melhores resultados que os sujeitos com lesões corticais mais subcorticais uni ou bilateral no exame neurológico (p = 0,0484 Teste de Mann-Whitney), função motora fina (p = 0,0200 Teste de Mann-Whitney), função sensorial (p = 0,0141 Teste de Mann-Whitney) e percepção (p = 0,0489 Teste de Mann-Whitney) / Abstract: The aim of the present study was to establish a relation between the performance of motor and sensory function in children with hemiparetic cerebral palsy (HCP) and the .findings in neurological imaging. Forty-six patients of both sexes were selected, 23 had pre or perinatal HCP (Group I) and 23 were normal (Group 11). The ages ranged ITom 7 to 16 years and the mean age was 12 years and 8 months. The BECKUNG (2000) protocols were used to assess the gross motor, muscular strength, movement amplitude and sensory functions, neurological assessment, fine motor function, sensory function and perception; the protocols of OKUMURAa,b et alo (1997) modified by PIOVESANA (1999) were used to evaluate the location and extent of injury in neurological imaging obtained by magnetic resonance (MR). The group I subjects were selected in a data bank ITom the Cerebral Palsy Ambulatory and evaluated in the physiotherapy and occupational therapy facility at the Children Neurological Center of the School of Medical Science of University of Campinas (UNICAMP). After the children parents signed a written informed consent, alI the subjects were clinically assessed through the proposed protocols. Exclusion criteria included: limiting musculoskeletal impairments, aci1te mental deficiency and visual and hearing impairment. The study design is descriptive and cross-sectional. The gathered information was stored in the data bank of the EPI-INFO 6.02 program for further statistical analysis. The evaluation of the motor and sensory function performance between the two groups was established through the Wilcoxon test for related samples. The tested group presented a slight mean dysfunction in alI the assessments: gross function (p < 0,001); fine motor function (p < 0,001); sensory function (p < 0,001); neurological assessment (p < 0,001); perception (p < 0,0002). The Mann-Whitney and Kruskal-Wallis tests were used to compare continuous and ordering measures between different groups. When the motor and sensory function performances between the categories were compared and related to the extent of the injury, the subjects that had only one injured brain side presented better performance of the gross function when compared to those that had bilateral injuries (p < 0,0122 Kruskal-Wallis test). The neurological assessment analysis showed that the subjects with only one injured structure presented better results than those with two wounded brain structures and bilateral injuries (p = 0,0066 Kruskal-Wallis test). In group I the subjects with only one injured brain structure presented better results in fine motor function than those attained ith two injured brain structures (p = 0,02755 Kruskal-Wallis test). When the motor and sensorial functions were related to the site of the injury, the subjects that presented the best results were those had subcortical injuries when compared to those that had cortical and sub cortical injuries in one or both sides of the brain: neurological assessment (p= 0,0484 Mann-Whitney test), fine motor function (p= 0,0200 Mann-Whitney test), sensory function (p= 0,0141 Mann-Whitney test), and perception (p=O,0489 Mann-Whitney) / Doutorado / Ciencias Biomedicas / Doutor em Ciências Biomédicas

Submitted by Heitor Rapela Medeiros (heitor.rapela@ufpe.br) on 2015-03-05T18:02:53Z No. of bitstreams: 2 DissertacaoFINALMarcelaMoreira.pdf: 3971308 bytes, checksum: 0c40bfcb0f18a7640075d47bb667a20d (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-05T18:02:53Z (GMT). No. of bitstreams: 2 DissertacaoFINALMarcelaMoreira.pdf: 3971308 bytes, checksum: 0c40bfcb0f18a7640075d47bb667a20d (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2012-07-06 / A deficiência do controle postural e mobilidade funcional é uma grande barreira encontrada pelas crianças com Paralisia Cerebral (PC), dificultando a sua independência em atividades de vida diária. Além disso, normalmente essas crianças necessitam frequentar por longos períodos os serviços de reabilitação e requerem grande empenho pessoal, familiar e dos terapeutas para a melhora do seu desempenho motor. Em vista disso, são necessárias novas intervenções terapêuticas visando uma maior motivação dessas crianças durante as sessões de fisioterapia e isso acredita-se ser conseguido com a RV. Objetivo: Avaliar a utilização da Realidade Virtual através do uso do videogame Nintendo Wii (Nintendo®) para auxiliar na melhora do controle postural e da mobilidade funcional de crianças com PC. Materiais e Métodos: Realizou-se um estudo piloto envolvendo 12 crianças com diagnóstico de PC de 6 a 10 anos, divididas aleatoriamente em dois grupos: intervenção (n=6) ou controle (n=6). A mobilidade funcional foi avaliada através do Gross Motor Function Measure (GMFM) e o controle postural foi avaliado através do Software de Avaliação Postural (SAPO) e da Plataforma de Força (EMG System do Brasil®). Em seguida, as crianças do grupo intervenção foram submetidas à terapia com Nintendo Wii (Nintendo®) com a Wii Balance board (Nintendo®), enquanto o grupo controle foi submetido à intervenção fisioterapêutica. Os grupos foram submetidos a 16 sessões, 2 vezes por semana. Resultados: Os grupos não apresentaram diferenças estatísticas significativas no que diz respeito às avaliações com SAPO, GMFM e Plataforma de Força. Conclusão: Os resultados, apesar da ausência de diferença estatística, sugerem que os indivíduos de uma maneira geral após o período proposto de intervenção, ainda se apresentam desalinhados, entretanto, pelos dados absolutos encontrados com a plataforma de força, eles se encontraram mais centrais e mais estáveis. Essas pequenas mudanças apesar de não serem estatisticamente significativas, aparentemente conseguiram ser transferidas para as suas atividades funcionais, a partir da verificação do aumento dos escores do GMFM. Essas mudanças podem não ter ocorrido de forma estatisticamente significativa, devido ao tempo insuficiente de intervenção e ao tamanho da amostra.

M.A. (Psychology) / Please refer to full text to view abstract

A través de la simulación numérica de la mecánica de aneurismas cerebrales, el profesor Dr. Ing. Álvaro Valencia del Departamento de Ingeniería Mecánica de la Universidad de Chile, en el marco del segundo año de desarrollo del proyecto Fondecyt ’FLOW DYNAMICS AND ARTERIAL WALL INTERACTION IN REALISTIC CEREBRAL ANEURYSM MODELS’, está desarrollando una metodología de apoyo a las decisiones médicas, donde las simulaciones computacionales puedan brindar un grado mayor de certidumbre en el diagnóstico y evaluación de este tipo de patologías. Producto de este trabajo, se cuenta con una metodología consolidada para la reconstrucción de casos de aneurismas cerebrales reales y para la realización de simulaciones de mecánica de sólidos, para el estudio de aneurismas cerebrales sin tratamiento. Por otro lado, el efecto del tratamiento de un aneurisma, desde el punto de vista mecánico, es un punto aún no abordado. A grandes rasgos existen dos tipos de tratamientos de aneurismas: la cirugía convencional, y el tratamiento endovascular. ´ Este ´ultimo busca modificar la circulación de sangre en el aneurisma para evitar su ruptura. En esta memoria de título se modeló y simuló un modelo de tratamiento endovascular tipo stent, que consiste en introducir una malla trenzada de metal flexible dentro de la arteria portadora del aneurisma, y se realizó una comparación de los resultados obtenidos de la simulación con el modelo de stent con los obtenidos previo al tratamiento, en el contexto de las simulaciones de mecánica de sólidos. Se observó que el stent no tuvo efectos importantes en variables como el esfuerzo efectivo (diferencia del 1% aproximadamente entre el caso sin tratamiento y el caso con stent) en la zona del aneurisma. Los estiramientos principales aumentaron con la inclusión del stent en el saco aneurisma, sin embargo, estos se homogenizaron y disminuyeron grandes magnitudes localizadas en la zona del cuello. La rigidez extra, proporcionada por el stent a la pared arterial hizo disminuir de forma importante el desplazamiento en zonas centrales y el domo del aneurisma.

Doctor en Bioquímica / En la neocorteza de mamíferos, la transición de progenitores neurales a neuronas de proyección y la mantención de la identidad neuronal recaen en la combinación de programas genéticos y epigenéticos que modulan eventos celulares como salida del ciclo celular, migración y diferenciación en neuronas funcionales. Estudios in vitro e in silico han mostrado que CoREST (REST Corepressor-1) es un factor importante en la coordinación de cambios de la estructura de la cromatina y actividad de genes durante la neurogénesis. CoREST es un componente fundamental de complejos de represión transcripcional y contribuye al ensamblaje de la maquinaria de remodelamiento de la cromatina en genes asociados con la identidad celular de progenitores neuronales y con la adquisición del fenotipo celular apropiado. CoREST puede formar complejos con diferentes proteínas como REST/NRSF, Nurr1, Tlx, Hsf1 y Znf198 (entre otras). Ejerce su función a través de enzimas que introducen modificaciones post traduccionales en las histonas, tales como la demetilasa de histonas específica de lisinas, LSD1 y las histonas desacetilasas, HDAC 1/2. Sin embargo, no existían estudios asociados al papel de CoREST sobre la neurogénesis durante el desarrollo. En esta tesis, se realiza un análisis de la función in vivo de CoREST. Estudios de inmunofluorescencia revelaron que CoREST está ampliamente expresado en la corteza cerebral durante el desarrollo y en etapas postnatales. Se utilizó la estrategia de electroporación in utero para introducir plasmidios que codifican horquillas cortas de RNA (shRNA) contra CoREST y así disminuir su expresión en progenitores neuronales localizados en la zona ventricular telencefálica. Esta aproximación reveló que la disminución de CoREST produce una alteración en la migración radial neuronal y a la vez cambios en la morfología. La inmunodetección de proteínas asociadas con distintos estadios de diferenciación celular no evidenció alteraciones en la adquisición del fenotipo neuronal (neuronas Tuj1+ y Vglut+), ni cambios significativos sobre la proliferación o sobrevida celular. En contraste, se observó un aumento en la proporción de progenitores neuronales Sox2+ y Tbr2+. Para profundizar en estos hallazgos, se realizaron experimentos de rescate utilizando variantes truncadas de CoREST para explorar cual dominio era relevante para recuperar la posición normal de las neuronas en la corteza. En estos experimentos el shRNA contra CoREST fue co-electroporado con el vector que codifica cada versión truncada de CoREST. La pérdida de función de CoREST fue revertida por una construcción desprovista del dominio de interacción con REST/NRSF (región N-terminal). Al mismo tiempo, la disminución en la expresión de REST/NRSF no generó perturbaciones significativas del desarrollo de las neuronas de projección. Por otra parte, la variante de CoREST carente del dominio de interacción con LSD1 (región C-terminal) no rescató el defecto en el posicionamiento neuronal causado por la disminución de CoREST. En estas condiciones experimentales, los datos presentados muestran que la función de CoREST en asociación con LSD1, pero no con REST/NRSF es requerida durante la ejecución del programa de desarrollo de las neuronas de projección. / In the developing mammalian neocortex, the transition from proliferating neural progenitors to projection neurons and the maintenance of neuronal identity relies on genetic and epigenetic programs that combine to establish the cell cycle exit, migration and differentiation into mature neurons. The in vitro evidence and biochemical data show that a key factor in the coordination of changes of chromatin structure and gene activity during neurogenesis is REST Corepressor-1 (CoREST). CoREST is a component of transcriptional repression complexes, contributing to the assembly of chromatin remodeling machinery at genes related with neural progenitors identity and cell fate decisions. CoREST can form complexes with different partners as REST/NRSF, Nurr1, Tlx, HSF1 and Znf198, and exerts its function through chromatin modifying enzymes, such as HDAC1/2 and LSD1. However, to date, no data had reported an effect of CoREST on neurogenesis during embryonic development. Here, the first functional in-vivo study of CoREST, it was detected that CoREST is widely expressed in the cerebral cortex during development and adulthood. It was used in utero electroporation of short hairpin RNA (shRNA) constructs into neuronal progenitors located in the cortical ventricular zone to knockdown CoREST. This approach revealed that radial migration of CoREST-deficient neurons is altered as well as their morphology. The neuronal identity of CoREST-knocked-down cells was unchanged (Tuj1+, Vglut+). By contrast, it was observed an increase of Sox2+ and Tbr2+ neural progenitor proportion without noticeable effect on cell proliferation and cell survival. To extend these findings, it was performed rescue experiments to examine the ability of distinct CoREST truncated versions to recover the normal neuronal position into the cortex. In these experiments, the plasmids encoding the CoREST truncated versions were co-electroporated with the shRNA vector targeting CoREST. CoREST loss of function was rescued by a construct lacking the characterized domain of interaction with REST/NRSF (N-terminal region). In addition, the loss of expression of REST/NRSF did not associate to significant perturbations of projection neuron development. On the other hand, CoREST truncated form which lacks the LSD1 interacting domain (C-terminal region) failed to rescue the migratory defects caused by CoREST knockdown. Under this experimental approach, the data presented here show that CoREST function in association with LSD1, but not with REST/NRSF is required for the expression of the physiological developmental program of projection neurons. / Fondap, Fondecyt

Background: Cerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia/reperfusion. Methods: We used a mouse model of middle cerebral artery occlusion (MCAO) to examine the therapeutic potential and mechanisms of neuroprotection by etifoxine. Results: TSPO was upregulated in Iba1(+) or CD11b(+) CD45(int) cells from mice subjected to MCAO and reperfusion. Etifoxine significantly attenuated neurodeficits and infarct volume after MCAO and reperfusion. The attenuation was pronounced in mice subjected to 30, 60, or 90 min MCAO. Etifoxine reduced production of pro-inflammatory factors in the ischemic brain. In addition, etifoxine treatment led to decreased expression of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase by microglia. Notably, the benefit of etifoxine against brain infarction was ablated in mice depleted of microglia using a colony-stimulating factor 1 receptor inhibitor. Conclusions: These findings indicate that the TSPO agonist, etifoxine, reduces neuroinflammation and brain injury after ischemia/reperfusion. The therapeutic potential of targeting TSPO requires further investigations in ischemic stroke.

A Rehabilitation centre for children with cerebral palsy is the proposed project undertaken in this dissertation. This theme was chosen after the author had been involved with New Hope School in fundraising projects for the past 3 years. The author recognized the need of a dedicated rehabilitation facility for children with cerebral palsy as well as better accommodation for rehabilitation purposes. Spending time with cerebral palsied children, the need for basic education becomes evident. Over protectiveness from parents could prevent these children from sensory experiences, which can only be evolved through touching, smelling, seeing hearing and tasting. This early childhood experience of sensory development usually involves play. Play is the ultimate form of exploration for any child and when disabled, free play is usually non-associative with everyday activities. Without free play, children will have a handicap in natural development of social, mental, physical and sensory skills. Through harmless play, even a lion cub learns to become a hunter. The aim of this project would be to create a center where play would be used to rehabilitate children with cerebral palsy. New Hope School is situated in the Menlopark area, Pretoria. The proposed site for the rehabilitation centre would be consolidated to the north western corner of the existing school grounds and thus engaging this project as an addition to the existing New Hope School. The architecture used, should be of simplistic nature which merges the interiors of the building with nature. By achieving this, the children would get a basic form of sensory development while rehabilitating in the building. Copyright / Dissertation (MArch(Prof))--University of Pretoria, 2010. / Architecture / unrestricted

No description available.

The most widely accepted hypotheses suggest that general anaesthetics interrupt conscious processes in the brain by decreasing synaptic excitation or by potentiating synaptic inhibition, especially in the neocortex. The putative transmitters in the neurological systems that generate neocortical arousal include acetylcholine, glutamate and γ-aminobutyrate (GABA). The primary objective here was to determine the neuronal mechanisms by which anaesthetics may obtund this arousal. The majority of the investigations were carried out on pyramidal neurons in layers IV and V of guinea pig neocortex (in vitro slices), using intracellular recording and pharmacological, including microiontophoretic, techniques. Bath applications of structurally dissimilar anaesthetics, isoflurane - a halogenated ether, and Althesin - a steroidal preparation, in concentrations of 0.5-2.5 minimum alveolar concentration (MAC) and 10-1300 μM, respectively, produced a small hyperpolarization (3-5 mV) which was associated with an increase in input conductance (10-30%). The lower concentrations (0.5-1.5 MAC and 10-200 μM) of these agents which are most relevant to the production of unconsciousness did not significantly affect the passive membrane properties. However, they produced striking decreases in spontaneous activities and the repetitive spike firing evoked by orthodromic (electrical) stimulation or intracellular current injections. Because the observed changes in membrane properties could not explain the reduction in neuronal excitability, the effects of anaesthetics were investigated extensively on excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs). The application of isoflurane or Althesin induced a dose-dependent, reversible depression in the amplitude of EPSPs, with EC₅₀s of 1 MAC and ~50 μM, respectively. The IPSPs also were reduced in a dose-dependent manner. In order to eliminate possible shunting of the EPSPs by the GABA-activated Cl-conductance that produces the IPSP in the observed EPSP-IPSP sequence, a GABA[symbol omitted]-antagonist, bicuculline, was additionally applied. Despite this IPSP-blockade, the anaesthetics strongly depressed the EPSPs as well as epileptiform activities evoked by subpial electrical stimulation. In cognizance of the possibility that a postsynaptic attenuation of responsiveness to transmitter substances may be involved in the EPSP depression, the neuronal sensitivities to acetylcholine, glutamate. and GABA were determined. Anaesthetic administration markedly reduced the depolarizations and associated conductance changes evoked by dendritic applications of acetylcholine, glutamate and N-methyl-D-aspartate (NMDA). The hyperpolarizing responses to somatic applications of GABA were not affected significantly whereas the depolarizing effects observed with its dendritic application were slightly depressed. Same degree of selectivity also was evident from the lower EC₅₀s for the isoflurane- and Althesin-induced depressions of responses to acetylcholine compared with glutamate. Under in vitro conditions of hypomagnesia the responses to acetylcholine were totally blocked and the order of depression in the responses to GABA and glutamate was reversed; this may be of importance in the mechanism for the known increase in anaesthetic requirements in clinical syndromes associated with hypomagnesaemia. Because the genesis of synaptic transients is affected by Ca²⁺ influx or disposition, the interactions of anaesthetics were investigated on spike afterhyperpolarizations (AHPs). The AHPs which are produced specifically by a Ca²⁺ -activated K⁺ -conductance were suppressed by the anaesthetics in a dose-dependent manner under conditions where contaminating IPSPs had been blocked by bicuculline. Since the passive membrane properties were unaffected, an interference with a transmembrane Ca⁺ -influx may be involved in the anaesthetic actions. The effects of anaesthetics on glutamate-induced and voltage-dependent increases in intraneuronal Ca²⁺ ([Ca²⁺]i) were determined in cultured hippocampal neurons with a Ca-sensitive probe (Fura-2) and microspectro- fluorometric techniques. Isoflurane application depressed the increases in [Ca²⁺]i. produced by application of glutamate under conditions where its actions would be favoured at NMDA- and quisqualate-subtypes of receptors. K⁺ -induced increases in [Ca²⁺]i also were reduced by application of isoflurane, probably due to actions on voltage-dependent Ca-channels in the membrane. These investigations have provided evidence for the first time that excitatory transmitter actions in neocortex are selectively depressed by anaesthesia. A plausible mechanism would include suppression of the postsynaptic Ca-conductances associated with the AHPs and glutamatergic, as well as cholinergic interactions at pre- and post-synaptic sites on neurons involved in neocortical arousal. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate